Passive Cavitation Image-Guided Ultrasound-Mediated Drug Delivery for Atheroma Th

被动空化图像引导超声介导的动脉粥样硬化药物输送

• 批准号: 8155319
• 负责人: Kevin Joseph Haworth
• 金额: $ 5.35万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8155319
• 关键词: Accounting; Acoustics; Air; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Arteries; Atherosclerosis; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cause of Death; Cessation of life; Clinical; Contrast Media; Cyclodextrins; Development; Direct Costs; Disease; Dose; Drug Delivery Systems; Drug Formulations; Elements; Encapsulated; Exposure to; Facilities and Administrative Costs; Family suidae; Feedback; Frequencies; Funding; Gases; Genes; Goals; Health Sciences; Image; In Vitro; Laboratories; Lipid Bilayers; Liposomes; Liquid substance; Maps; Measurement; Measures; Mechanical Stress; Mediating; Methods; Metric; Microbubbles; Modeling; Monitor; National Heart, Lung, and Blood Institute; Nature; Performance; Pharmaceutical Preparations; Phospholipids; Physiologic pulse; Physiological; Protocols documentation; Research; Scheme; Signal Transduction; Site; Solutions; Spatial Distribution; Staging; Techniques; Testing; Texas; Theoretical model; Therapeutic; Therapeutic Agents; Tissues; Translations; Ultrasonic Transducer; Ultrasonography; United States; United States National Institutes of Health; Universities; Use of New Techniques; Vascular Diseases; Vesicle; Work; aqueous; base; detector; improved; innovation; mortality; prevent; public health relevance; rosiglitazone; targeted delivery

DESCRIPTION (provided by applicant): Traditional means to identify and treat arterial disease are hampered by an inability to localize atheroma extent and composition. New techniques using targeted echogenic liposomes (ELIP) are being explored as possible solutions to overcome these problems. ELIP are phospholipid vesicles enclosing both aqueous and gaseous spaces. Therapeutics, such as drugs or genes, can be loaded into the ELIP. Furthermore, it has been seen that upon exposure to pulsed ultrasound, the therapeutic can be released from the ELIP and made available for delivery to nearby tissue. The encapsulated gas allows the ELIP to be imaged with a clinical ultrasound scanner and the therapeutic to be delivered via cavitation nucleation. The principal aim of this proposal is to develop techniques that will provide spatially resolved, noninvasive feedback for ultrasound-mediated delivery of a therapeutic to an arterial wall using ELIP. To achieve this aim, two specific aims will be investigated. 1) The acoustic emissions of insonified ELIP, as recorded by a passive ultrasound array, will be correlated with release of an anti-inflammatory (rosiglitazone-cyclodextrin). Subsequently, a spatial map of the emissions, and correlated therapeutic release, will be created. 2) Passive imaging of the insonified ELIP will be correlated with the delivery of the therapeutic to an ex vivo porcine artery. Successful completion of these studies will contribute significantly to the long-term goals of the Holland and McPherson Labs at the Universities of Cincinnati and Texas Health Sciences Center-Houston to trigger and enhance the delivery of a therapeutic for improved physiologic cardiovascular flow. PUBLIC HEALTH RELEVANCE: The proposal seeks to develop passive cavitation images for ultrasound-mediated local release and enhanced delivery of an anti-inflammatory drug for atheroma treatment using echogenic liposomes.

描述（由申请人提供）：传统的识别和治疗动脉疾病的方法由于无法定位动脉粥样硬化的范围和组成而受到阻碍。使用靶向回声脂质体（ELIP）的新技术正在被探索作为克服这些问题的可能解决方案。ELIP是包围水和气体空间的磷脂囊泡。治疗方法，如药物或基因，可以加载到ELIP。此外，已经看到，暴露于脉冲超声后，治疗可以从ELIP释放，并可用于输送到附近的组织。被封装的气体允许临床超声扫描仪对ELIP成像，并通过空化成核提供治疗。本提案的主要目的是开发一种技术，该技术将为使用ELIP的超声介导的治疗药物输送到动脉壁提供空间分辨、无创反馈。为实现这一目标，将研究两个具体目标。1)无源超声阵列记录的非静音ELIP的声发射将与消炎药（罗格列酮-环糊精）的释放相关。随后，释放的空间地图，以及相关的治疗释放，将被创建。2)非超声ELIP的被动成像将与治疗药物在离体猪动脉的输送相关。这些研究的成功完成将对辛辛那提大学的Holland和McPherson实验室和德克萨斯健康科学中心休斯顿的长期目标做出重大贡献，以触发和加强改善生理性心血管血流的治疗方法的交付。